Valvular regurgitation is a serious and at times life-threatening condition that occurs commonly in heart disease. Its presence and severity have a critical impact on clinical decision-making, but present techniques for their noninvasive assessment by color Doppler echocardiography of the turbulent jet are empirical, semi-quantitative, and widely variable due to physical and physiologic factors. The goal of this proposal is therefore to address the hypothesis that application of basic physical principles can provide a non-invasive means of quantifying regurgitant flows velocities that can be directly measured by Doppler echocardiography, specifically based on conservation of mass within the laminar ventricular flow field proximal to the regurgitant orifice. This approach initially assumed that flow converges in a uniform radial manner towards the regurgitant orifice, forming concentric hemispherical isovelocity shells imaged by Doppler. The major obstacle to clinical application of this technique is that widely different results are obtained when flow rate is calculated at different distance from the orifice on the flow map because isovelocity shells close to and far from the orifice are not hemispherical, and may never be truly hemispherical for non-circular orifices. Therefore, the specific hypothesis of this study is that a technique can be devised based on mathematical analysis of the proximal flow field that can determine the optimal alias velocities (or isovelocity contours) at which flow rate can be calculated most accurately, to permit clinical applications. This technique and a modification using an adaptable hemi-elliptical fit to the surface area have shown promising initial results in vivo and in vitro. Specific aims of the proposal are to determine whether simple modifications of these algorithms based on color flow images can provide accurate results in several realistic situations similar to those encountered clinically, including non-circular orifices, orifices within non-planar leaflet geometries, superimposed ventricular, outflow, variable chamber confinement, and realistic orifice geometries and physiologies, such as prolapse and ischemic mitral regurgitation. We also plan to test whether applying this algorithm at multiple time points can integrate total regurgitant volume and display the time-course of effective regurgitant orifice area (instantaneous flow rate/velocity) as a guide to the pathophysiology of the regurgitant lesion and its response to therapy. The approach will include complementary in vitro and in vivo studies in models of mitral and aortic insufficiency, including ventricular models with excised mitral valves, allowing comparisons with laser Doppler anemometry and computational modelling to refine the technique, and in vivo models providing known flow rates with a realistic environment and geometries similar to those in patients. The improved accuracy of the method, combined with the objectivity of the quantitative algorithm, should yield results of immediate impact for clinical decision-making, with analysis that can potentially be automated for convenient application with existing equipment. Improved accuracy could provide a stronger basis for testing how quantitative measures of the regurgitant lesion can best be combined with measures of chamber size and function to predict outcome, response to therapy, and optimal timing of intervention.